Pressure ventilation leads to the elaboration of a circulating negative inotrope (s). We propose to use several separation techniques to isolate and identify a biologically active fraction. We have recently been able to equate contractility and Ca ions-ATPase activity in rat cardiac subfractions. This bioassay requires only 0.1 ml plasma. The importance of other negative inotropes, such as thromboxane B2, will be tested by radioimmunoassay of the plasma of PEEP treated subjects. We will also evaluate the role of microaggregates formed in-vivo as mediators of cardiopulmonary failure. These microaggregates will be measured in mixed venous and arterial blood using a glutaraldehyde fixative that stabilizes the cells and allows them to be counted using a Coulter technique. We will measure microaggregates during endotoxemia, aspiration pneumonia (3 ml/kg of 0.1 N HCl) and abdominal aortic aneurysm surgery. We plan to relate the pulmonary generation of the antiaggregating and aggregating prostaglandins to circulating levels of cathepsins, phagocytic capability and lymphocytic response to PHA stimulation.